FMRP is the protein product of the human FMR1 locus. Mutations at this locus which prevent expression of active protein cause Fragile X Mental Retardation. This protein binds to RNA and is found associated with polyribosomes. FMRP is alternately splices and closely related homologs are coded on autosomal chromosomes. An understanding of the role of FMRP requires structural information, as well as information about the expression, localization, and half-life of this family of proteins. This project will examine the structure and stability of FMRP and other family members. Specific aims are: 1) to produce and characterize biochemically useful amount of recombinant FMRP family members, splice variant, and mutants; 2) to determine the structure of FMRP and an FMRP-RNA complex; 3) to produce a panel of isozyme specific antibodies in order to unambiguously determine the identity and localization of expressed FMRP isoforms; 4) to determine the mechanism and rate of intracellular FMRP degradation.